Induction of the CBP transcriptional co-activator early during laryngeal carcinogenesis

摘要

Purpose: CREB-binding protein (CBP) is a transcriptional "integrator" that is suspected of contributing to tumorigenesis. This is the first systematic morphologic study evaluating CBP expression in a large series of human laryngeal tissues containing normal epithelium, premalignant lesions (hyperplasia and/or dysplasia), and squamous cell carcinoma. Methods: Immunohistochemical methodology was performed on formalin-fixed paraffin-embedded sections by using a monoclonal anti-CBP antibody. CBP expression was screened and compared in 156 patients with various laryngeal histologic entities. Results: Nuclear expression of CBP was found in 44 out of 91 (48.4%) specimens with normal-appearing epithelium (46.2% weak and only 2.2% moderate positivity), 92 out of 100 (92%) with hyperplastic lesions (56% weak, 36% moderate/strong, and only 8% no positivity), 80 out of 103 (77.7%) with dysplastic lesions (45.6% weak, 32.1% moderate/strong, and 22.3% no positivity), 37 out of 45 (82.2%) with well-differentiated carcinoma (42.2% weak, 40% moderate/strong, and 17.8% no positivity), 31 out of 43 (72.1%) with moderately differentiated carcinoma (32.6% weak, 39.5% moderate/strong, and 27.9% no positivity) and eight out of 12 (66.7%) with poorly differentiated carcinoma (41.7% weak, 25% moderate/strong, and 33.3% no positivity). Statistical analysis and correlation of the intensity of nuclear immunostaining among the various histologic entities revealed statistically significant results. Conclusions: Overexpression of CBP is detected from the very early stages of laryngeal carcinogenesis, suggesting that CBP may play a role in malignant transformation of precancerous laryngeal lesions. It is possible that overexpression of this protein is a prerequisite for the observed p53 upregulation in premalignant lesions, implying an indirect role of CBP in p53-mediated tumorigenic potential.